Abstract

Colorectal cancer is highly metastatic. In a quarter of patients with tumors of this type, liver metastases are detected already at the time of diagnosis. Therefore, the search for drugs that can reduce the metastatic activity of cells is an important task. A tumor experiences constant stress, resulting in an increased activity of the transcription factor HSF1, which is able to trigger the synthesis of heat shock proteins. This increases the resistance of cancer cells to both stress and antitumor therapy. It has been shown recently that HSF1 plays a critical role in the process of the epithelial–mesenchymal transition (EMT) underling the formation of metastases. Here, we show that a new inhibitor of HSF1 activity, CL-43, is capable of suppressing EMT that is induced by TGFβ1. CL-43 significantly reduced the migration and proliferative potency of DLD1 cells treated with TGFβ1. Analysis of vimentin level showed that cell treatment with CL-43 cells reduced this EMT marker and returned the expression and localization of E-cadherin in the cells to the original pattern. These findings suggest that CL-43 has therapeutic potential for treatment of colorectal tumors.

中文翻译：

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CL-43，HSF1活性的新抑制剂，抑制DLD1结肠癌细胞的上皮-间质转化

摘要

大肠癌是高度转移性的。在四分之一的这种类型的肿瘤患者中，在诊断时已经检测到肝转移。因此，寻找可以降低细胞转移活性的药物是一项重要的任务。肿瘤承受不断的压力，导致转录因子HSF1的活性增加，从而能够触发热激蛋白的合成。这增加了癌细胞对压力和抗肿瘤治疗的抵抗力。最近发现，HSF1在上皮-间质转化（EMT）的过程中起着至关重要的作用，是转移形成的基础。在这里，我们显示了一种新的HSF1活性抑制剂CL-43，能够抑制TGFβ1诱导的EMT。CL-43显着降低了用TGFβ1处理的DLD1细胞的迁移和增殖能力。波形蛋白水平的分析表明，用CL-43细胞进行的细胞处理降低了该EMT标记，并使E-钙粘着蛋白在细胞中的表达和定位恢复到原始模式。这些发现表明CL-43具有治疗结直肠肿瘤的治疗潜力。